The hunt for HIV infection blockers

Nov. 6, 2003

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By BARBARA BERG

Drs. Shiu-lok Hu, from the University of Washington, and Julie Overbaugh, shown in Overbaugh's Human Biology lab, will collaborate with local researchers to identify targets for a vaccine that could prevent infection from HIV, the virus that causes AIDS.

Photo by Todd Mcnaught

Researchers in the Human Biology Division and colleagues at the University of Washington and the Seattle Biomedical Research Institute (SBRI) have received a $15 million grant to identify promising new vaccines to prevent infection from HIV, the virus that causes AIDS.

Dr. Shiu-lok Hu, professor of pharmaceutics at the University of Washington, will lead the four-and-a-half year project, which is funded by the National Institute of Allergy and Infectious Diseases. Co-investigators include Dr. Julie Overbaugh in Human Biology, and Drs. Nancy Haigwood and Leonidas Stamatatos of the Seattle Biomedical Research Institute.

Overbaugh said the goal of the grant is to find new approaches for developing candidate vaccines that elicit neutralizing antibody responses.

"Most vaccines currently in the pipeline are designed to elicit an immune response from T cells," she said. "While these vaccines can slow disease progression, they don't block infection. In order to do that, a vaccine needs to trigger a protective antibody response."

To identify vaccine candidates likely to provoke a protective antibody response, Overbaugh will rely on a collection of blood samples that she and colleagues have accumulated from a large study of viral transmission in HIV-infected women in Kenya.

"The idea is to base a vaccine on a strain of HIV that is representative of what is prevalent among infected individuals in Africa, where the epidemic is most severe," she said. "We can examine the blood samples we've collected both to characterize the particular strain of the virus that has infected each woman and to measure her antibody response. We think it makes sense to build a vaccine from a viral strain that is already good at provoking an antibody response."

Because these natural antibody responses are not protective against infection, Overbaugh said that her collaborators at UW and SBRI will focus on modifying the viral strains her group identifies to make them more effective at eliciting protective antibodies. This will involve introducing a combination of subtle mutations and some deletions into the virus, using the structure of the virus as a guide. These changes will be examined for their ability to provoke a better immune response. The UW group will then test the optimized immunogens in various combinations, using state-of-the-art delivery systems.

"Our goal is to have the most promising candidates we identify be rigorously tested in animal models within five years and to then select those that look promising for clinical trials in humans," she said.

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